Stem Cell-based Therapies for Amyotrophic Lateral Sclerosis:

More than just another symptome treating medicine

Anova IRM Stem Cell Treatment for:
Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS) is caused by the progressive death of cerebral (upper) and spinal (lower) motor neurons. It is a complex disease which involves the activation of several cellular pathways in both neurons and glial cells (Figure 1). This results in a severe motor dysfunction muscles become atrophic due to the lack of nerve stimulation. Often, the origin of the disease is unknown. ALS is not a typical autoimmune disorder, since autoimmune and inflammatory abnormalities are not the cause of the disease, even though they influence its progression.

The therapeutic strategy used for treating ALS is aimed at protecting neurons from degeneration, and to stimulate cell regeneration. However, currently there is no drug treatment that can restore neural cells.

Stem Cell Therapy (SCT), is a promising, novel strategy that combines neuroprotection and recovery of neuromotorial function. A study by Mazzini et al. demonstrated that the procedure of ex vivo expansion of autologous Mesenchymal Stem Cells (MSCs) and of transplantation into the spinal cord of humans are safe and well tolerated by ALS patients. A more recent study, by the same group, however, confirmed that MSC transplantation into the spinal cord of ALS patients is not only safe, but might also serve as a treatment option for future cell-based clinical trials for the treatment of ALS (Figure 2).

Many current preclinical studies suggest that stem cell transplantation has the best effect when aimed towards protecting, rather than replacing or repairing the motor neurons of ALS patients. We offer novel, highly advanced, safe and efficient stem cell-based treatments (Anova Stem Cell Secretome) for treating patients with ALS. For more information, please feel free to contact us.

Biological perspective (on the cellular level) of ALS:
Why Stem Cells have huge potential to help?

Stem Cell ALS 10Figure 1: shows the complexity of ALS, which involves many different pathways in motor neurons and neighboring glia. Microglia (bottom part) activate an inflammatory cascade via MCP-1 secretion. Astrocytes (purple cells) contribute to the injury of motor neurons through various mechanisms, including release of inflammatory mediators such as NO and PGE2 (left), reduced expression and activity of the glutamate transporter (right), reduced lactate release (top left) and activation of pro-NGF–p75 receptor signaling (left). Motor neurons also undergo abnormal RNA processing which, together with overproduction of reactive oxygen species (ROS), contribute to protein misfolding (center). Misfolded proteins can form aggregates, leading to cellular stress and ultimately activate autophagy and apoptotic pathways. Two major components of motor neuron injury are mitochondrial impairment and dysregulation of calcium handling (top middle) which also stimulate the apoptotic cascade. Impaired axonal transport (left bottom) may contribute to an energy deficit, disturbing normal functionality (distal axonopathy). Abbreviations: EAAT2, excitatory amino acid transporter 2; ER, endoplasmic reticulum; IL, interleukin; MCP-1, monocyte chemoattractant protein 1; NGF, nerve growth factor; NO, nitric oxide; PGE2, prostaglandin E2.

The Stem Cell Secretome therapy for Amyotrophic Lateral Sclerosis (ALS)

Several clinical trials with stem cells for ALS are ongoing. As usual during studies, new insights imerge. The ANOVA-IRM stem cell therapy is a product of the latest insights to what actually causes the stem cell therapies to be effective and concentrating on these factors. ANOVA-IRM stem cell therapy for Amyotrophic Lateral Sclerosis (ALS) employs mesenchymal stem cells (MSC) secretome for a variety of reasons.
As explaind in detail in our for Professionals section, MSCs secrete many trophic (e.g.SDF-1α, indoleamine-2,3-dioxygenase,prostaglandin E2, TGF-β1, HGF, IL-4, IL-6 and IL-10, SCF, LIF, FGF-2, VEGF, IL-6, VEGF, Neurotrophin-3 (NT3), SDF-1α,EGF and BDNF) and neuroprotective factors (e.g. NGF, GDNF and BDNF). Additionally, among the Micro vesicles secreted from the MSC, are the very important exosomes caring information loads by means of microRNAs (miR-29a, miR-9, miR-124, miR-145). Also, exposure of neurons and astrocytes with MSC secreted exosomes leads to an increase of miR-133b which was shown to promote functional neurological recovery.
The Anova Secretome method is designed to harness these and many other factors in the count of tens of billions in a unique lab designed process using GMP methods.

References and Literature - Stem Cell-based Therapies and Amyotrophic Lateral Sclerosis (Click for more)

  1. Wijesekera, Lokesh C., and P. Nigel Leigh. "Amyotrophic lateral sclerosis." Orphanet journal of rare diseases 4.1 (2009): 3.
  2. Ferraiuolo, Laura, et al. "Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis." Nature Reviews Neurology 7.11 (2011): 616-630.
  3. Mazzini, Letizia, et al. "Stem cell therapy in amyotrophic lateral sclerosis: a methodological approach in humans." Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders 4.3 (2003): 158-161.
  4. Mazzini, L., et al. "Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A Phase I clinical trial." Experimental neurology 223.1 (2010): 229-237.
  5. Papadeas, Sophia T., and Nicholas J. Maragakis. "Advances in stem cell research for Amyotrophic Lateral Sclerosis." Current opinion in Biotechnology 20.5 (2009): 545-551.
  6. Janson, C. G., et al. "Human intrathecal transplantation of peripheral blood stem cells in amyotrophic lateral sclerosis." Journal of hematotherapy & stem cell research 10.6 (2001): 913-915.
  7. Thomsen, Gretchen M., et al. "The past, present and future of stem cell clinical trials for ALS." Experimental neurology 262 (2014): 127-137
  8. Staff, Nathan P., et al. "Safety of intrathecal autologous adipose-derived mesenchymal stromal cells in patients with ALS." Neurology 87.21 (2016): 2230-2234.
  9. Oh, Ki-Wook, et al. "Phase I Trial of Repeated Intrathecal Autologous Bone Marrow Derived Mesenchymal Stromal Cells in Amyotrophic Lateral Sclerosis." Stem cells translational medicine 4.6 (2015): 590-597.
  10. Petrou, Panayiota, et al. "Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials." JAMA neurology 73.3 (2016): 337-344.
  11. Farinazzo, Alessia, et al. "Murine adipose-derived mesenchymal stromal cell vesicles: in vitro clues for neuroprotective and neuroregenerative approaches." Cytotherapy 17.5 (2015): 571-578.
  12. Bonafede, Roberta, et al. "Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis." Experimental cell research 340.1 (2016): 150-158.
  13. Boruczkowski, D., et al. "Mesenchymal Stem Cells As A Therapeutic Option For Patients With ALS." Gen Med (Los Angel) 4.235 (2016): 2.

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